Acne Vulgaris is an inflammatory disease of the skin, caused by changes in the pilosebaceous units (skin structures consisting of a hair follicle and its associated sebaceous gland). Acne develops as a result of blockages in follicles. Hyperkeratinization and formation of a plug of keratin and sebum (a microcomedo) is the earliest change. Enlargement of sebaceous glands and an increase in sebum production occur with increased androgen (DHEA-S) production at adrenarche. The microcomedo may enlarge to form an open comedo (blackhead) or closed comedo (whitehead). In these conditions the naturally occurring largely commensual bacteria Propionibacterium acnes can cause inflammation, leading to inflammatory lesions (papules, infected pustules, or nodules) in the dermis around the microcomedo or comedo, which results in redness and may result in scarring or hyperpigmentation. See, e.g., Webster GF (2002), “Acne vulgaris,” BMJ 325 (7362): 475-9, PMID 12202330.
Benzoyl peroxide (“BPO”) has been widely used for the treatment of acne. Gel or cream containing benzoyl peroxide is usually rubbed into the pores over the affected region. In addition to its therapeutic effect as a keratolytic (a chemical that dissolves the keratin plugging the pores), benzoyl peroxide also prevents new lesions by killing P. acnes. Benzoyl peroxide has the advantage of being a strong oxidizer and thus does not appear to generate bacterial resistance. However, the disadvantage associated with the use of benzoyl peroxide is that it routinely causes dryness, local irritation and redness.
Additionally, compositions containing benzoyl peroxide for topical treatment of acne are available primarily in cream, lotion gel and ointment forms. Rubbing creams or ointments into the skin is inherently inefficient and difficult to achieve a constant and balanced application over large area of skin. Lotions on the other hand are not ideal as they can run and drip and may not be homogenous. Therefore, while semi-solid compositions, such as creams, gels and ointments are commonly used by consumers, new forms are desirable in order to achieve better control of the application, while maintaining or bestowing the skin beneficial properties of such products. Hence, the development of new compositions, having breakable foam consistency when released from a container and liquid properties when applied onto the skin is advantageous. Further, the development of new foamable compositions that can reduce or diminish the dryness and irritation associated with the use of benzoyl peroxide is especially desirable. Benzoyl peroxide is a sensitive active agent which reacts readily and degrades for example in oil. As a powerful oxidant, it can cause the breakdown of other active agents such as certain antibiotics if present in the same formulation and is itself sensitive to formulation conditions which have different values. Hence, there is a need to provide foamable compositions in which benzoyl peroxide is stable in the presence of other excipients.
Whilst it may be predictable to add a moisturizing agent to a BPO formulation to counter the drying effect of BPO this per se is not sufficient to prevent dryness. Identifying formulations in which BPO remains stable and homogenous that are able to improve skin moisture rapidly and effectively on application to the skin is a challenge.
Foams and, in particular, foam emulsions are complex dispersion systems which do not form under all circumstances. Slight shifts in foam emulsion composition, such as by the addition of active ingredients, may destabilize the foam. Foams are very complex and sensitive systems and are not formed at will. Mere addition of basic ingredients like oil, water, surfactant and propellant is far from sufficient to produce foams of quality that are homogenous, stable, breakable upon mechanical force and can be used to provide a shelf stable pharmaceutical or cosmetic composition. Small deviations may lead to foam collapse. Much consideration needs to be given to facilitate the introduction of an active agent, such as examining compatibility and non reactivity with the various excipients and container and determining shelf life chemical stability.
Neubourg (US 2006/0099151), for example, notes that the stability of foam is strongly dependent on the specific composition of the foam forming components, so that even small deviations in the composition may lead to a collapse of the foam. Gordon et al. (U.S. Pat. No. 3,456,052). also teaches that one cannot generate a good quality foam by simply adding a propellant to a mixture of components: